Tag Archives: B12 Deficiency

My mom has not been well. Not eating well, massive head ache, lost a lot of weight. Blood test results yesterday showed that she’s B12 deficient; urine, however, has too much protein. Any idea why?

I suppose, since he asked me, it most likely meant her MD didn’t offer an explanation for the test results. One this is sure, neither she nor he knew what to do. My feeling is that he asked just in case I knew anything that could help. And I did. So, I did.

Let’s go through the analysis together:

Is it normal to have protein in the urine? What is supposed to be excreted in the urine? What organ regulates what goes and what doesn’t go into the urine? Under what circumstances would protein end up in the urine?

From a biological standpoint protein is precious. From an evolutionary standpoint protein is hard to come by and hence relatively rare. Therefore, the body has evolved to use and keep as much protein as it can. The urine is intended to excrete uric acid, which is the main acid produced by metabolic processes. Urine is excreted through the urethra, it is stored in the bladder, and it is produced by the kidneys, which filter the acids out of the blood. The kidneys try to prevent large molecules like amino acids and glucose from going through into the urine. The solids in the blood are separated from the water, the acid is filtered out of it, and depending on the state of hydration, more or less water is used to make urine or returned back to the blood. The only circumstances under which protein would end up in the urine are 1) that the kidneys are not working properly, and unable to filter the protein out of the blood, 2) that there is a serious excess of protein in the blood, or 3) that there is both kidney dysfunction and excess amino acids in the blood. We’ve explored kidney function in great detail before in The kidney: evolutionary marvel, and this understanding comes from there.

This means we already know that his mom either has kidney disease, that there is too much protein in the blood, or both. But he wrote that she had lost a lot of weight. Losing weight can be due to fat loss, muscle loss, or both. Usually, very rapid weight loss in the elderly is not voluntary, and almost always means rapid loss of fat and muscle. Therefore, for sure, the protein in the urine was the result of a the fast weight loss with rapid breakdown of muscle tissue.

But why? Why would she all of a sudden start losing weight so fast? What could have happened or triggered this?

Well, he also wrote that she was found to be B12 deficient. And if this was recognized by the conventional MD who ordered the tests, you can be sure B12 levels were very low: surely below 200 pg/ml.

Do we become B12 deficient all of a sudden? Or do B12 levels decrease slowly and gradually over the years? Can we even become B12 deficient all of a sudden? Why do we become B12 deficient in the first place? And why is B12 important and relevant in this case?

It is possible to become B12 deficient all of a sudden. This happens when our levels are marginally acceptable to start, and we receive a large dose of an anesthetic, before a surgery, for example. Anaesthetic drugs deplete B12; and the larger the dose, the more severe the depletion. But this is certainly not the majority of cases.

Most of the time, B12 levels decrease slowly and gradually over the years, either from inadequate intake, or from compromised digestion. In the younger population, it is usually from inadequate intake—as is the case for vegans and vegetarians. In older adults, it is usually from compromised digestion—as is the case from the middle aged to the elderly, generally from a damaged gut and stomach cells that do not produce enough hydrochloric acid needed to break down the protein we eat.

As some of you will remember, we’ve also explored the importance and functions of vitamin B12 in B12: your life depends on it and more recently in Case Study: Homocysteine, B12, and folate. Vitamin B12 is most important for its role in the nervous system: for healthy nerves and proper brain function. But it is also an important anabolic nutrient essential in building and preserving muscle tissue. Bodybuilders everywhere have been taking B12 supplements for at least 4 decades, exactly because it’s a potent natural anabolic.

Therefore, here is where our analysis leads us:

The most probable explanation is that his mother has been growing more and more deficient over the years, a B12 deficiency developed over several decades that just recently reached critically low levels. This triggered rapid weight loss that caused both the loss of body fat stores and the breakdown of muscle tissue. The fat loss released streams of toxins that have been accumulating in the fat cells over years and years, and which caused the massive head aches from which she was complaining. The muscle loss, the rapid breakdown of muscle tissue due to the extreme B12 deficiency, caused the kidneys to be overwhelmed and become unable to keep all these amino acids in circulation, and the protein therefore spilled into the urine.

My recommendation: B12 shots of 1 mg once a week for 10 weeks, and then of 5 mg once a month for the rest of her life.

The story doesn’t end here. It turns out that she has osteoarthritis and she’s in pain. Some time ago some friends of hers recommended taking vitamin D supplements, and so she did. When she got her blood test done, her 25-OH-D was through the roof at 127 ng/ml. If you’ve read our last post on vitamin K2 you will know that this is possibly the worst thing that someone with arthritis can do: high levels of D without correspondingly high levels of K2 will accelerate soft tissue calcification. And since osteoarthritis is a disease of calcification, it will make everything much worse than it already is. Naturally, I immediately recommend she stop taking vitamin D and start taking large doses of vitamin K2 as soon as possible, before something more serious like a stroke or a heart attack happens.

He sent me the blood tests, which I examined to get a better picture. Interestingly, few markers were out of the reference ranges. This is probably why nobody said anything other than to point out the obvious abnormalities: low B12, high D, and protein in the urine.

But in addition, what could be seen was that both urea and creatinine were near the top of their range, which is expected from rapid weight (muscle) loss, and the eGFR (the estimated glomerular filtration rate) was at the low end of the reference range, which is expected from compromised kidney function given the protein in the urine. C-reactive protein was high but not super high. This signals system inflammation, and is naturally excepted for someone with arthritis, as we also have seen together in the past (https://healthfully.net/category/arthritis/). Lastly, calcium was also high, but nevertheless within the reference range, something we would expected for someone with high D and not enough K2.

I asked if she was taking medications, and she was. Several different drugs among which were a statin drug to lower cholesterol, a malaria drug used to treat symptoms of arthritis, and a couple of high blood pressure drugs one that is a diuretic and forces the kidneys to excrete more water, and the other that is an angiotensin antagonist that blocks the hormone which tells the kidneys to retain water when hydration is inadequate. I replayed my view that drugs typically always attempt to block some pathway, and prevent the body from doing something that it naturally does to protect itself. And in this case, she should wean herself off all of these over a few weeks.

I also explained that one of the most serious side effects of statin drugs is that they cause muscle wasting, promoting muscle tissue breakdown. Statins do this in everyone, but in the elderly who already have accelerated muscle breakdown, it can be very serious.

My final recommendations, beside coming off the various drugs gradually to avoid a shock to the body, were as simple as possible for an old woman to follow: high dose B12 shots, high dose K2 pills, and high dose Mg as L-threonate, plenty of water and salt each day, a low carb diet rich in animal fats and green veggies, and sodium bicarbonate in water first thing in the morning on an empty stomach. We’ll see what happens.

Blood tests can be used very effectively as a window onto the inner environment of the body. MDs tend to only pay attention to the markers outside the reference range that appear in bold on the print outs. But the reference range is derived from the blood tests of the whole population, and the population is far from being optimally healthy, that’s for sure. What we need are not reference ranges derived from a sickly population, but an understanding of how the body works, what its organs and systems are trying to do, and with that understanding, of what our blood markers should be … ideally. What they should be in the best possible case.

That’s what we have to aim for. And that’s what we have to learn to do, because we certainly can’t rely on your average MD to help us in this. If you are an MD, and you are reading this, you already know that you are not your average MD, and I’m pretty confident you also know that your patients are lucky to have you.

Like this:

Homocysteine is an amino acid that occurs in the body as an intermediate in the metabolism of methionine and cysteine. Folic acid is a vitamin of the B complex, found especially in leafy green vegetables, liver and kidney. (Both these definitions are from the New Oxford American Dictionary on my MacBook.) Folic acid is B9, and folate is a salt of folic acid, but the two names are used interchangeably.

Homocysteine is normally broken down and recycled so that it doesn’t accumulate. This relies on sufficient amounts of vitamins B12, B6 and B9 being available to facilitate this process. Homocysteine, abbreviated Hcy, is a highly inflammatory substance associated with much higher risks of cardiovascular events. Research (AHJ 2004) has shown that rHcy causes endothelial dysfunction and damage, accelerates thrombin formation, inhibits native thrombolysis, promotes lipid peroxidation through free radicle formation and induces vascular smooth muscle proliferation and monocyte chemotaxis.

Naturally, we should strive to keep Hcy levels in our blood as low as possible. There is no healthy minimum for it. In other words, the lower the better. And conversely, the higher its concentration, the worse off you are in terms of the potential for damage to the arteries and cardiovascular events. For a detailed look at Hcy in relation to vascular disease, read this article by Dr Neville Wilson, (thanks Ivor Cummins).

Last week I explained something about Hcy, B12, and folate to my son who was getting ready to go back to university for his second year (studying Philosophy and Modern History at St-Andrews). Afterwards, I thought it would be useful to share this with you, and I started working on this post.

This story is drawn from my own personal history. It is a case study with me as the primary subject using data I have collected from regular blood tests over these last seven years. However, I also use data from both my mother’s and my son’s blood test results that happen to be critical for understanding my own blood test results. Below, I describe the whole story and analysis of the data in detail. If you are not interested in the details, the punchline is this:

If your homocysteine levels are high, you should supplement with B12 and fully active folate in order to ensure the body has what it needs to process it. Some people lack the enzyme needed to activate the folic acid we get from food. This prevents the body from breaking down homocysteine that consequently accumulates in the blood. This is a genetically transmitted trait, which I think I have inherited and transmitted to my son. Because of it, we must supplement with activated folate to ensure breakdown of Hcy.

The first time I read about Hcy was many years in Anthony Colpo’s book The Great Cholesterol Con. The subject was discussed towards the end of the book in a short chapter, but I was left with a strong impression. Colpo emphasized that Hcy—unlike cholesterol—was a good predictor for heart disease. And it wasn’t just good: it was one of the best. But this wasn’t the only reason it made such an impression on me.

The first time I got my Hcy levels checked was on August 27 in 2012. The result was 18.3 micromol per litre. On the results, the reference range was 5 to 15; moderately elevated was 15 to 30; and elevated was indicated as anything greater than 30 micromol per litre. Beside the middle range, it was written vitamin deficiency in parentheses. But it wasn’t written what vitamin deficiency would cause elevated Hcy. The doctor from whom I had requested the test didn’t know either. (As you might have experienced for yourself, most MDs don’t really know much when it comes to blood test results.)

I had already started supplementing with B12 by that time. Most of us, as vegetarians, quickly and usually angrily dismiss nutritional advice or warnings of potential problems from deficiencies that non-vegetarians love to offer when they find out we don’t eat meat. We usually interpret these as justifications of their feelings of guilt for not being vegetarians themselves. At least I know I did when I was vegetarian. Although most people who do give their unsolicited advice are rarely knowledgeable in the subject matter, I now know that I was dead wrong about my quick dismissal of several things in relation to dangerous deficiencies that come about when we eliminate meat and animal products from our diet. Vitamin B12 is surely the best example.

It was after reading this article on B12 by Mercola that I came to realize how disastrous were the consequences of living with low levels of B12, and in my case, how disastrous were the consequences of having been vegetarian for 20 years. I started supplementing right away, and got my first B12 blood test a few months later in 2010 on September 8. The result was 271 pg/ml. According to the lab who did the test, this was within range. But I knew it wasn’t. I knew this was much too low, and that I desperately needed to correct this as fast as possible, stop and hopefully reverse the neurological degradation associated with my long-standing B12 deficiency.

In that article was also underlined the connection between low B12 and high Hcy levels. It read: Cardiovascular and cerebrovascular diseases have a common risk factor – increased homocysteine levels in blood. Studies show insufficient amounts of folic acid and vitamin B12 can elevate your homocysteine levels, potentially increasing your risk for heart disease and stroke. So, of course I was worried. I was also angry at myself for having been so stupid and stubborn all these years… these 20 long years. But at least I now knew what I had to do: I needed to boost B12 levels and keep them high.

And I did. Look at how my B12 levels evolved over 7 years:

Blood B12 levels measured over seven years since September 2010.

Does seeing this make you wonder how the Hcy levels evolved? My expectation was that Hcy would drop as B12 rose. With some time delay of course, but still: as B12 levels increased, homocysteine concentration would decrease. Here is what happened:

Blood homocysteine levels measured over five years since August 2012.

Not so obvious to interpret, right?

Let’s look at all the tests in which both B12 and Hcy were measured, and plot them one against the other. It’s called a correlation plot, and this is what we find:

Homocysteine plotted against B12. Data point numbe labels show chronological order of tests.

So, there clearly is an inverse relationship between levels of Hcy and B12. There is no doubt in this. But at least for me, it’s not very tight. The correlation coefficient and the uncertainty on it quantify this relationship.

The coefficient can have any value between -1.0 and 1.0: a value of 1.0 signifies perfect correlation; a value of -1.0 signified perfect anti-correlation; and a value of 0 signifies that there is no correlation at all. The uncertainty on the coefficient quantifies how well the coefficient is determined from the data points, and therefore how loosely or tightly they are spread around the overall trend in the data set.

A coefficient of -0.66, as we found, tells us that there is indeed an anti-correlation in the relationship between Hcy and B12 concentrations. The uncertainty of 0.22 tells us that the correlation is not so tight. And when we look at two time series above, we see that although B12 has been above 600 pg/ml since 2014, Hcy levels remained more or less flat until the end of 2016.

My initial interpretation was that because I had been B12 deficient for basically 20 years, correcting that long-standing deficiency, and repairing the damage caused by it to the body and in particular to the nervous system, required maintaining consistently high levels of B12 for a long time, allowing the body the time needed to repair itself: two decades of B12 deficiency could obviously not be corrected in a few months. Maybe it was only after these 7 years of intensive B12 supplementation that the positive results were beginning to manifest themselves in this way.

And by intensive, I mean pretty serious. I started taking oral supplements of 2000 mcg per day; then transitioned to patches which are more effective because the B12 is absorbed directly through the skin without having to go through the digestive system; and finally moved on in early 2015 to monthly intramuscular injections of 5000 mcg of methycobalamin. Nevertheless, Hcy remained pretty much the same, even after months of injections. What was going on? Why wasn’t Hcy dropping?

Maybe you are thinking that there might be another way we could use to check how much influence B12 levels have on Hcy? Well, I have something I think is quite remarkable to share with you.

At the very end of July 2014, I brought my mother to a specialized blood analysis clinic, and ordered the complete set of tests listed on my essential blood test reference sheet. The results came back a few days later: her B12 was at 292 pg/ml; her folic acid was at 11.6 ng/ml; and her Hcy was at 30.5 micromol/l. She was 82 and, just for the record, it was the first time in her life that her B12 and Hcy levels had been measured in a blood test.

I immediately got a friend of hers and ex-nurse to give her methylcobalamin injections a couple of times a week. Five weeks later in early September we repeated the test for homocysteine. The result was 9.5!

My 82 year old mother’s homocysteine levels went from 30.5 to 9.5 micromol/l in 5 weeks following 10 injections of 1 mg doses of methylcobalamin B12.

She was out of the red. At least on that front. Hcy of 9.5 micromol/l is still moderately elevated when we consider that we would ideally have none. But 30.5 was dangerously high. This, to my mind, is strongly indicative of the crucial importance and immediate effect of vitamin B12 on homocysteine metabolism.

It wasn’t a tightly controlled experiment where everything was kept the same except the one variable under investigation, which in this case would have been the B12 injections. It wasn’t, because my mother did also at the same time adopt a new dietary regimen, following an alkalizing, very low carb, low protein, high fat, intermittent fasting cleansing protocol I had designed for her, that also included quite a number of other supplements. All were food supplements: vitamins A-D-K2, niacinamide, co-enzyme Q10 as ubiquinol, phospholipids as sunflower lecithin, omega-3s as krill oil, turmeric extract, tulsi extract, chlorella and spirulina, magnesium, zinc, iodine, etc.

Certainly it is true that everything influences everything else, but there’s no question in my mind that as far as homocysteine was concerned, the most important element in this protocol was the intramuscular injection of methylcobalamin approximately every three days. There is also no question that achieving such a drop in Hcy levels at such an advanced age and in so little time is nothing short of amazing.

The point of my retelling of this was to present direct evidence of the strength of the relationship between B12 levels and Hcy concentration. I think it does. Obviously, you are to draw your own conclusions.

Coming back to my case, in the fall of 2013 I stumbled uponThe Complete Blood Test Blueprintin which Joseph Williams, a knowledgeable, experienced, and kind MD, was interviewed by Kevin Gianni, the host of Renegade Health, in a series of interviews that covered a large number of blood tests in great detail. I learned a lot things listening to Dr Williams. Admittedly, I was disappointed by the lipid panel discussion, and in particular by the discussion of cholesterol and lipoproteins. But putting this aside, I was generally very impressed.

Dr Williams talked about B12 deficiency at length, but I was already well versed in the subject by that time. I had recently read the book Could it be B12?, made detailed notes of it, and then posted for you B12: your life depends on it. Dr Williams also talked about Hcy. In that discussion was mention of the fact that in addition to B12 (cobalamin), B6 (pyridoxine) and particularly B9 (folic acid) were also essential for breaking down Hcy. I didn’t really think much of it, simply because my diet was and always had been rich in leafy greens, which naturally ensured a high intake of folic acid.

A few years and several blood tests later, I listened to the interviews again. And this time, something caught my attention in the part on homocysteine that hadn’t the first time: it was mentioned, in passing towards the end of the discussion, that some genetically predisposed people lacked the enzymes needed to activate folic acid; and that these people therefore needed to supplement with the already active form of B9 called tetrahydrofolicacid.

It caught my attention because by that time I had several measurements of Hcy that, even with my continued and even intensified B12 supplementation, were not showing evidence of going down. Remember: I started injections in early 2015. But there was something else that made this comment stand out for me: my son’s recent blood test results.

In July 2016 I brought my son to get a complete blood test that comprised all the markers I usually test for, together with all the major hormones, in order to have a baseline for him in his prime. It is certainly true that we can talk about optimal levels for each of the hormones we know and can test for. But our own personal ideal hormonal profile is unique to us. And the best time to get a baseline is when we are 18 years old: full grown adults at our youngest.

Laurent’s B12 was 578 pg/ml, his folic acid was 23 ng/ml, and his Hcy was 10.9 micromol/l. At 18, having had no major health issues, no accidents or serious diseases, a remarkably healthful fresh, green, organic, low carb, high fat diet of unprocessed whole foods for most of his life, I thought that this slightly elevated Hcy could be due to one of three things: either his body was still B12 deficient and just slowly building up its B12 stores, even though the three of us had all started with supplementation and patches at the same time; he was one of these people Dr Williams had made reference to who lacked the enzyme to activate folate, and therefore couldn’t effectively break down Hcy; or both.

I immediately ordered activated folate for us, and we started taking it in August 2016. If you take a look at the second plot that shows my Hcy levels as a function of time, you can see that it was just around 18 micromol/l at the end of July. And half a year later, towards the end of 2016, my Hcy level was the lowest it had ever been. Obviously, I was very happy to see this major improvement in achieving a drop in Hcy, something I had been trying to do for so many years. Therefore, also obviously, I continued taking activated folate. As you can see from the next two data points in 2017, Hcy was measured at 10 and then 8 micromol/l. We haven’t made another blood test to check Laurent’s levels. We’ll do that around Christmas at the end of this year when he comes back for the holidays.

Can we see how strong the relation between folate and Hcy actually is? We can plot the measurements we have one against the other like we did above for B12 and Hcy. What we find is this:

Homocysteine plotted against folate. Data point number labels show chronological order of tests. Arrows mark upper limits.

The relationship is very clear and linear. But I have to admit that I have cheated your eye a little bit. The measurements of folic acid are capped at 24: any value above that is simply reported as greater than 24. This was the case in tests (4), (8), (9), and (10). I show this with little arrows pointing towards higher values. Because the last three measurements were so close together in time, for the sake of clarity in the plot, I placed them at 25, 26 and 27, inversely proportional to the Hcy level. This is why they appear to follow the line. Otherwise, they would be at on the left edge of the arrows, one on top of the other, aligned with point (4), all at 24 on the x-axis. Note that I also plotted my son’s results (labelled as such), adding a data point at (23, 11).

What can we conclude from this investigation? Well, it isn’t totally clear cut and straight forward. I admit. But let’s review the facts:

For me:

I was 38 years old at the time of my first B12 test.

My B12 levels were low for 20 years: 270 pg/ml when first tested after few months of supplementation.

My Hcy levels were high at 18 micromol/l about two years after starting B12 supplementation.

B12 is necessary to break down Hcy.

It took me 3 years of oral and patch B12 supplementation to reach 600 pg/ml.

In early 2015 I started monthly B12 injections.

Only after almost 2 years of injections did my Hcy levels drop below 10 micromol/l.

But this precipitous drop in Hcy was concurrent with the start of supplementation with activated folate.

For my mother:

She was 82 years old at the time of her first B12 test.

Her Hcy levels were very high at 30 micromol/l.

Her B12 levels were low for who knows how long: 292 pg/ml when first tested.

She received approximately 10 injections of 1 mg in five weeks.

Her homocysteine levels dropped from 30 to 9.5 micromol/l.

For my son:

He was 18 years old at the time of his first B12 test.

His homocysteine levels were moderately high at 11 micromol/l.

His B12 levels were 578 pg/ml.

In addition to this, we have the plots above that show inverse relationships both between Hcy and B12, and between Hcy and folic acid. From this, there are at least three very clear conclusions we can draw:

Low levels of B12 are associated with high levels of homocysteine,

Higher levels of b12 are associated with lower levels of homocysteine, and

Raising B12 levels leads to a decrease in homocysteine concentration.

At this stage and with the data we currently have, going further is more speculative. But here is what I think:

I am one of these people that lacks the enzymes to activate folic acid.

I might have inherited this trait from my mother or from my dad (considering how well she responded to intensive B12 therapy), and it was probably transmitted to my son.

I was B12 deficient, and correcting this deficiency didn’t lower my Hcy levels.

It was only when I started taking activated folate supplements that Hcy levels dropped quickly and significantly.

The reason I think this comes from two lines of reasoning. The first is that, as I just mentioned, it is only when I started taking activated folate that my Hcy levels dropped below 10 for the first time in seven years since the start of B12 supplementation.

The second is that even though both my mother and I were definitely B12 deficient, both probably for a long time, and that this would necessarily have led to an accumulation of Hcy in the blood that would have been greater in her case than in mine due to her age; my son was only 18 years old, and could not have been B12 deficient, at least not for almost 10 years. Nevertheless his Hcy levels were moderately elevated.

This is what I told him the other day. It took me only 5 minutes to tell him; it has taken me a lot longer to write this post. But I think the details are important if we are to understand things well. And by this I mean know what we understand, and know what we do not understand; know what conclusions we can make, and know what is hypothesis or speculation.

It’s not possible to be sure at this stage. We need more data and more experiments. But it’s not easy to gather such data, just because it takes a long time and strong commitments to be consistent with a supplementation programme over months and often years. If you have similar data and are willing to share, I would be happy to take a look at them.

Data like these trace and reveal so much about what’s happening inside our body, below the skin, far deeper than our eyes can see. But we can only begin to understand these measurements and the processes that drive their evolution by spending the time to look at them in detail. This is what we did here together. I hope you found it interesting.

Do you know what are your blood levels of homocysteine, B12, and folate? If not, you better get that checked out.

Cobalamin, that we call vitamin B12, is without any doubt one of the most important micronutrients. However, very few people, and unfortunately, also very few doctors, know this, and even when they do know, they very rarely truly appreciate the extent to which B12 deficiency can be detrimental.

Today, I will tell you why B12 is so important, what happens when there is B12 deficiency and why it is so widespread, and finally, what we can and should do about it, as individuals, but more specifically with what concerns us here, to help maintain a healthy workforce. I will do this in 10 minutes.

Before we get into it, I want to highlight that maybe the biggest difficulties we, as a society, have, but have to overcome for the benefit of the population on a large scale, is that even though many doctors have learnt that B12 deficiency can be extremely grave, they believe it is rare and that systematic testing is not necessary. This is very unfortunate, and it is this attitude that causes, on the one hand,

Why B12 is so important?

B12 is essential at three fundamental levels: cellular energy metabolism, gene transcription, and nervous system function. Cobalamin’s vital role at the cellular level is not restricted to only some tissues and organs: it is vital for every cell of every tissue and every organ. In relation to the nervous system, both for the central nervous system—our brain—and the peripheral nervous system—the spine and entire network of nerves connected to the brain and coursing through the whole body—vitamin B12 is essential in building, maintaining and repairing the myelin sheath that covers the nerves to ensure protection and proper signalling. It is, in fact, the consequences of B12 deficiency on the nervous system—an array of neurological issues—that most often betray this very serious problem.

What happens when it is deficient?

Now just ask yourself what you think would happen if the myelin sheath that covers all the nerves throughout the body were to deteriorate?

At the cellular level, every cell becomes unable to adequately produce energy, be it from glucose or from fat. We can easily extrapolate and imagine what it would mean for the organism as a whole to have a lack of, or severe debility in the energy available to it at the cellular level, and this, for the trillions of cells of which it is made. This would have a most profound effect on everything that we do, and everything that the body does throughout the day and night.

Now consider a yet deeper level: in the nucleus of every cell, where genes are protected and cared for, a problem in the very transcription and replication of genes—these delicate operations that are necessary and vital for the continual renewal, repair and reproduction of cells—which must and do take place throughout our life, this long succession of infinitesimal instants, the perception of which is almost universally absent from consciousness, but for which the timescale is, in fact, very long at the cellular level, where movements and interactions take place at phenomenal speeds. Vitamin B12 is absolutely essential for this too. And if it’s missing? Unintended, unplanned, and unwanted genetic mutations. This means problems: very serious problems.

Why is deficiency so common?

There are two reasons for cobalamin deficiency: inadequate intake and inadequate digestion. Although the former is indeed quite important, it is the latter that causes B12 deficiency to be so common, and in fact, quasi-universal.

Cobalamin is produced in the gut of animals by specific bacteria that make part of the intestinal flora. Even if this can also be true for humans, we have relied on animals, both by eating them and products derived from them like eggs and dairy, for millions of years of evolution as hominids. In animal foods, cobalamin is always bound to protein from which it needs to be separated in order to be used. This, in turn, can only be done starting in the highly acidic environment of a well functioning stomach that secretes enough hydrochloric acid, but also enough Intrinsic Factor as well as pepsin.

Cobalamin is carried into the duodenum—the first part of the small intestine—by salivary B12 receptors that are then broken down by pancreatic protease. This allows the free B12 to attach to Intrinsic Factor, and make its way to the ileum—the very last part of the small intestine—where it penetrates the mucosal wall for absorption. Finally, the free cobalamin latches onto the plasma transporter protein transcobalamin II whose function it is to carry the B12 to the cells throughout the body. Any excess, unneeded at any given time, is carried to the liver where it is stored.

The major problem is that almost 100% of the population has dysfunctional digestion: stomachs producing neither enough hydrochloric acid nor Intrinsic Factor and pepsin; pancreases producing neither enough bicarbonate solution needed to neutralise the acidic chyme from the stomach when it goes into the small intestine, nor enough enzymes essential for breaking down nutrients; and chronically acidic intestines coated with partially undigested food, especially putrefying protein, overtaken by pathogenic yeasts like candida, and with highly compromised intestinal walls that not only cannot properly absorb nutrients, but also cannot prevent toxins from leaking back into the bloodstream and body in general. Pretty scary, isn’t it?

So, what do you think happens to the excessively delicate and precarious chain of metabolic and biochemical steps necessary for the absorption of B12 in a tiny section of the very last part of the small intestine under these pretty dismal conditions? It breaks down. And what is the result? Quasi-universal B12 deficiency in all age groups, from infants to the elderly. Naturally, because the digestive organs tends to degrade with time, the older we get, the more deficient we become. And is it a surprise that all signs and symptoms of ageing that we all deem normal and inevitable are also all symptoms of B12 deficiency? No, not in the least.

What can be done about it?

Testing B12 status should be included in every blood test for everyone everywhere. We are still very far from this situation, however. Testing B12 status can literally save your life, but at the very least, save you from mostly permanent and possibly extremely debilitating neurological damage. It is most accurately done by measuring concentrations of serum B12, plasma Homocysteine (Hcy) and urinary methyl-malonic acid (MMA), but it is usually more than adequate to measure only B12 and Hcy in order to assess B12 status.

(Both Hcy and MMA are toxic byproducts of protein metabolism that must be converted to benign and/or useable forms by the action of B6, folic acid (B9) and especially B12. And by the way, Hcy, because of its highly toxic nature and damaging effect on blood vessels, happens to be the best marker of all for risk of cerebro- and cardio-vascular disease.)

Consequently, what we must generally do is to supplement to first raise and subsequently maintain optimal B12 levels. What are optimal B12 levels? Well, it is remarkable that on most blood test result sheets we see the “normal” B12 range starting at 200 or even 180 pg/ml, given that both neurological and psychiatric symptoms appear at levels below 450 pg/ml. The consensus between B12 experts is that levels should be above 600 and optimally between 800 and 2000 pg/ml. There are no reported cases of negative consequences of hyper-cobalaminia, nor of B12 overdose while supplementing with methylcobalamin, the right choice for supplementation. (See 1 and 2—a compilation of B12-related literature.)

What should we do about it?

Even though there is ample evidence and data of various studies showing how widespread B12 deficiency actually is, it would be good to have our own data, and therefore, our own grounds for further action and recommendations. For this we should just add the B12 and Hcy tests for every staff member (and encourage contractors to do the same), and compile and analyse these data. The data will be collected anonymously by the medical service. It will include—in addition to B12, Hcy, Total Blood Count and iron (which are standard)—age, gender, weight, height and waist circumference (to calculate BMI and ABSI).

The analysis, following the prescription of the biostatistician Royall (1997), and inspired by its application in an astrophysical context by Belanger (2013), can be carried out regularly, whenever additional data is available, until it becomes conclusive enough to stop gathering data.

At that point we would know beyond any doubt if it is the case that the workforce is generally (> 50%) B12 deficient (< 450 pg/ml), what actual fraction it is, and some other useful information that can be extracted from the data. We would then be able to formulate conclusions and, depending on the results, also recommendations for other establishments, and all of this, with the very simple but noble motivation of promoting health among our colleagues, friends and family members, not just now, but for the rest of their life.

(This is the transcript of a short presentation I gave on Friday November 22, 2013. The information is from my article B12: your life depends on it. If you enjoyed reading this article, please click “Like” and share it on your social networks. This is the only way I can know you appreciated it.)

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There are very few nutrients as crucial to our well-being as vitamin B12. The reason why this is so is that vitamin B12 is essential for cellular energy metabolism, gene transcription, and nervous system function. This vital role at the cellular level is not restricted to only some tissues and organs: it is vital for every single cell of every tissue and every organ.

For the nervous system, both for the central nervous system—our brain—and the peripheral nervous system—the spine and entire network of nerves connected to the brain and coursing through the whole body—vitamin B12 is essential in building, maintaining and repairing the myelin sheath that covers every nerve to ensure protection and proper nerve signalling. It is, in fact, the consequences of B12 deficiency on the nervous system that most often betray this very serious problem.

Everyone should supplement and maintain blood levels of B12 in the range from 600 to 2000 pg/ml in order to avoid and, if this is the case, help recover from the wide range of problems that result from B12 deficiency or insufficiency. Health care practitioners: this is the first thing you should check for every patient that comes in, independently of their age or condition.

What is vitamin B12 and how is it absorbed?

B12 or cobalamin is a large molecule whose central atom is cobalt, and around which are arranged various other compounds. To be active in the body, the cobalamin molecule must be in one of two enzyme forms: methylcobalamin or adenosylcobalamin, both of which must be in a charge state of +1. Even though cobalamin can exist in two other charge states, +2 and +3, neither of these is bio-active. Its most powerful antagonist is nitrous oxide (N2O; laughing gas), which continues to be commonly used as an anaesthetic agent during surgical operations, because it inactivates the molecule by modifying the cobalt ion from a charge state of +1 to one of either +2 or even +3.

Cobalamin is produced in the gut of animals by specific bacteria that make part of the intestinal flora. Although this can also be true for humans, we have mostly relied on animals both by eating them and products derived from them, like eggs and dairy. In animal foods, cobalamin is always bound to protein from which it needs to be separated in order to be used. This, in turn, can only be done starting in the highly acidic environment of a well functioning stomach that secretes enough hydrochloric acid, but also enough Intrinsic Factor and pepsin.

Cobalamin is carried into the duodenum—the first part of the small intestine—by salivary B12 receptors that are then broken down by pancreatic protease. This allows the free B12 to attach to Intrinsic Factor, and make its way to the ileum—the very last part of the small intestine—where it penetrates the mucosal wall for absorption. Finally, the free cobalamin latches onto the plasma transporter Protein Transcobalamin II whose function it is to carry it to the cells throughout the body. Any excess, unneeded at any given time, is carried to the liver where it is stored.

Where do we get B12?

That herbivores like sheep, goats and cows, which thrive when they eat only grass, do not suffer from B12 deficiency, but that most of us humans tend to (estimates from various large scale studies range between 40 and 80%), points to two key issues at the heart of this problem:

One, we have evolved and survived as a species over several million years by eating animals. It is believed by some that it was, in fact, the very eating of animal foods, maybe specifically bone marrow, which was, on the one hand, the only left overs after carnivore predators like lions, and then all other scavengers but predators for us like wolves and jackals had eaten all they could, and on the other, the only thing that only humans could get to by breaking apart the bones, that allowed the brain to grow in size over a relatively short evolutionary period, seting us apart from our our primate ancestors and cousins. Whatever the case may be, the organism of the human species as a whole grew accustomed and became reliant on an external supply of vitamin B12 from animal sources.

Two, it is most certainly the case that even with the healthiest, let’s even say ideal or perfect intestinal flora, as humans we will definitely have a very different flora than those of the herbivore animals we domesticated, and it will arguably always be much less capable and much less efficient at producing cobalamin from any of the plant foods we do eat. Moreover, if B12 is manufactured by some of the bacteria in our perfectly healthy colon—the large intestine, it will still not easily make it into circulation because, as we saw, absorption of cobalamin takes place in the ileum in the last part of the small intestine, which is upstream from the large intestine. The manufactured B12 would somehow have to migrate backwards from the colon to the ileum, a most likely very difficult thing to do.

The first point is supported by ample archeological, anthropological, as well as evolutionary biological evidence. In fact, it turns out that our hominid ancestors have most certainly lived for the bulk of our evolutionary history during periods of glaciation where the land over most of the Earth’s surface was covered in ice. This implies that there was a marked absence of plant life in most places on Earth, and therefore an absolute reliance on animals for survival, eating virtually only animals, which in turn also ate virtually only other animals and fish, which ate smaller fish, and on down the food chain to those feeding on sea-borne plant foods. The Inuits, who basically live on whale blubber, are the perfect example of such a scenario. But this could well have been the scenario for a lot of the humans that populated the Earth, and for a good portion of our history spanning the last 2.5 million years.

The second is hypothetical, but on firm footing given that it is indisputable that the gut flora of a herbivore will be different—substantially different—from ours, but also that we simply cannot survive for very long on greens alone as do sheep, goats, cows and all other herbivores. Furthermore, in actual fact, most humans have a dysfunctional digestive system, with heavily compromised and impaired intestinal flora. As a consequence, even those who eat adequate or even large amounts of B12-rich animal foods, usually cannot benefit from it because the cobalamin simply doesn’t make it into the bloodstream for any one of several possible impediments along the ingestion-breakdown-absorption chain.

This is not to say that our digestive flora cannot produce some B12 from plant-based foods, but the evidence shows us that it definitely cannot produce enough, whatever the reason: studies have shown that although B12 deficiency is of the order of 40% in the general omnivore population, it is 50% in vegetarians, and up to a staggering 80% in long-term vegans (see Chapter 6 of Could it be B12? and references therein).

Why is B12 deficiency such a big deal?

Well, let’s ask another question instead: What would happen if the myelin sheath that covers the nerves in our body—peripheral, spinal and brain—were to deteriorate?

At the cellular level, every cell would be unable to adequately produce energy, be it from glucose or from fat. We can easily extrapolate and imagine what it would mean for the organism as a whole to have a lack of, or severe debility in the energy available to it at the cellular level, and this, for the trillions of cells throughout. This would have a most profound effect on everything that we do, and everything that the body does throughout the day and night.

Now consider a yet deeper level: in the nucleus of every cell, where genes are protected and cared for, a problem in the very transcription and replication of genes—these delicate operations that are necessary and vital for the continual renewal, repair and reproduction of cells—which must and do take place throughout our life, this long succession of infinitesimal instants the perception of which is almost universally absent from consciousness, but for which the timescale is, in fact, very long at the cellular level, where movements and interactions take place at phenomenal speeds. Vitamin B12 is absolutely essential for this too. And if it’s missing? Unintended, unplanned, and unwanted genetic mutations from errors in transcription. This means problems; very serious problems.

Who should be concerned about all this?

The short answer is: everyone. This means you, but also your kids as well as your parents. It means infants, toddlers, children, teenagers, young adults, mature adults, the middle aged, the elderly, and the oldest among us: absolutely everyone.

For the longer answer, it would appear to be the case that we are, or at least should be, born with a good B12 reserve, and that, as it is used over time, the amount in the body and blood slowly decreases as the reserves get used up and eventually depleted. Some consider this to be the normal state of affairs. This inevitably implies that those at greatest risk of suffering from B12 deficiency are the oldest, and also that the older we get, the greater our chances of becoming victims of the effects of this deficiency. And this is indeed what we find: practically everyone above the age of 60 is B12 deficient, and more often than not, severely deficient (serum B12 < 200 pg/ml).

It is therefore not really surprising that every single behavioural characteristic—intellectual, psychological, emotional, physiological and physical—associated with ageing and its multiple manifestations in the elderly, senior moments in all their different forms: memory problems, disorientation, inability to concentrate or even pay attention, frailty, weakness, unsteadiness, loss of balance, etc, etc, are all typical symptoms of B12 deficiency.

Could it be that all these characteristics of old age are actually the characteristics of B12 deficiency? Could it be that if we didn’t let B12 levels drop below 600 pg/ml and actively maintained them around 1000 pg/ml throughout life, that seniors would simply not manifest any of these signs of old age? Maybe. Maybe even most probably. What an entirely different world it would be: strong and healthy, energetic and vibrant, sharp and alert old people. Sounds great, doesn’t it? And hard to imagine, isn’t it? But wouldn’t that be wonderful, for everyone, and especially for the elderly themselves?

As alluded to a moment ago, we should be born with a large B12 reserve. It is of particular importance that we need to have a plentiful supply of B12 throughout our development in the womb, during infancy, and up to the 7 years of age. Why is it so important? Because our nervous system develops fastest while we are in our mother’s womb, and then during infancy and as a toddler, until it reaches maturity by the time we are about 7, and because cobalamin is essential for this development.

The complication, however, a point of crucial importance, is that only B12 consumed by the pregnant mother at first, the breast-feeding mother afterwards, and finally by the toddler can be used to ensure an optimal development and building of a healthy brain and nervous system. Even if the mother had good B12 levels before, during and following pregnancy, only fresh B12 can be used in the developing child. So, if she doesn’t consume much or any during this critical period, the unborn child and infant will have only a meagre or non-existent supply of cobalamin, and consequently, impaired—often severely—brain and nervous system development.

This is a very serious matter. In fact, for many infants, it is a matter of life or death. Or just barely less dramatic but maybe even worse in some respects, it can make the difference between a normally healthy brain and nervous system, and permanent developmental disability, both physical and intellectual, right down to a full or partial vegetative state for a whole lifetime.

All of this shows why B12 deficiency tends to be not only transmitted, but to worsen in severity from one generation to the next, with all the negative consequences that come with it, but most notably those that affect the brain and all cognitive functions. Terribly sad and unfortunate as it is, numerous studies and reports on the babies of vegetarian but especially vegan and macrobiotic mothers have shown very serious neurological problems, developmental delays as severe as stunted brain growth and death, but also that even mild deficiencies in infancy are associated with seriously impaired cognitive performance in adolescence and adulthood. I cannot stress this enough: B12 deficiency is really very serious.

Now, between the oldest and the youngest there is everyone else. If we are born with an excellent B12 status, then we are lucky and likely to be able to make it to old age without any apparent problems in this regard. If we are born B12-deficient, then we are most certainly likely to suffer from it greatly, and this, much sooner than later. And if we are born with anything in between, an intermediately good or bad B12 status, then problems will appear later in life, or sooner, depending on many other factors, but most importantly on how much cobalamin we consume, and how well it is absorbed. Consequently, manifestations of cobalamin deficiency can appear at the age of a few months or a few years; as a child or teenager; as a young adult or person in their prime; near retirement or in old age; or it may also never become apparent. Unfortunately, this condition is continuously growing in importance, the people it affects growing in number, and the reported cases growing in severity.

Unfortunately, and extremely sadly for way too many people whose bodies, minds and lives are destroyed by an undiagnosed deficiency, B12 is not something that doctors routinely check or know much about. Most of them believe that it will appear in the total blood count (TBC) panel either as enlarged (megaloblastic anaemia) or fewer red blood cells (pernicious anaemia). But by the time you get there, you have been suffering the ravages of B12 deficiency for a while already, and have thus almost certainly also already suffered permanent neurological damage. So, for your sake, don’t wait for your doctor to notice this. Instead, teach them about it. You will be doing them and their patients an immense favour.

Closing with the good news

It is really easy to prevent and avoid becoming cobalamin deficient, but also to correct a deficiency that exists or even one that has persisted for several years or decades, no matter if you eat animal products or not, want to or not, think that you should or not. We must, very simply, check our B12 status regularly by measuring three markers—serum B12, plasmahomocysteine (Hcy), and urinary methyl-malonic acid (MMA)—and make sure to supplement in order to raise and maintain B12 levels in the range between 600 and 2000 pg/ml, with concentrations of Hcy and MMA as low as possible. Pregnant and nursing mothers should maintain levels above 1000 pg/ml to ensure healthy nervous system development in their children.

(Both Hcy and MMA are toxic byproducts of protein metabolism that must be converted to benign and/or useable forms, the animo acid methionine, for example, by the action of B6, folic acid (B9) and especially B12. Here is a good information-dense compilation of B12/Hcy/MMA publications, and transcript of an interview with John Dommisse, a psychiatrist and B12 expert, who published the above quoted serum B12 range as optimal in this authoritative paper cited in Could it be B12? where I read about it.)

Supplementation should be with methylcobalamin—not cyanocobalamin—and should be as aggressive as needed depending on the result of the assessment. In cases where B12 levels are below 200 pg/ml, we should request methylcobalamin injections to be administered daily for 5-6 days, and then weekly until B12 reaches 2000 pg/ml. It should be maintained there at least until Hcy and urinary MMA have dropped significantly, and then monitored and maintained around 1000 pg/ml.

For anything else between 200 and 600 pg/ml and/or elevated Hcy or MMA, methylcobalamin patches are an effective way to get B12 levels up. In addition, oral supplementation, although the least effective of the three, still works surprisingly well compared to other supplements, and obviously cannot possibly hurt; it can only help. I recommend doing both patches and oral supplements until levels are around 1000 pg/ml, and then maintaining them with either one.

Finally, and very important to know is that you cannot overdose on methylcobalamin B12: not one negative physiological side effect has been reported or is known from methylcobalamin supplementation. You cannot do yourself or anyone any harm by taking B12 as methylcobalamin in large quantities for a long time; you can only do yourself and others harm by allowing a deficiency, as mild as it may be, to develop or linger. This applies to everyone.

If you enjoyed reading this article, please click “Like” and share it on your social networks. This is the only way I can know you appreciated it.